This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Administrative Core Program Summary and Evaluation Overall Structure The Administrative Core has several missions, including overall organizational and scientific leadership, careful mentoring of the junior investigators, recruitment of new faculty, organizing of a seminar series in Immunology/Infectious Diseases, organizing COBRE retreats, and support of graduate students and postdoctoral fellows in COBRE laboratories. Progress on each of these areas is detailed below. Our current COBRE faculty include: Junior Faculty [unreadable]Beth D. Kirkpatrick, M.D. Innate Immune response to Cryptosporidium parvum [unreadable]Christopher Huston, M.D. Entamoeba Histolytica Phagocytosis and Inflammation. [unreadable]Mariana Matrajt, Ph.D. Subversion of Host Signaling by Toxoplasma gondii. [unreadable]Terrence Delaney, Ph.D. Regulation and Effectors of Plant Innate Immunity [unreadable]Jane Hill, Ph.D. Detection of aerosolized microbial products [unreadable]Jason Botten, Ph.D. (new faculty recruit) Immune response to arenaviruses and flaviviruses Senior Faculty [unreadable]Ralph C. Budd, M.D. - PI [unreadable]Gary Ward, Ph.D. [unreadable]Co-PI [unreadable]Jonathan Boyson, Ph.D. (former COBRE junior faculty) [unreadable]Elizabeth Bonney, M.D. [unreadable]Sally Huber, Ph.D. [unreadable]Mercedes Rincon, Ph.D. [unreadable]Cory Teuscher, Ph.D. [unreadable]Markus Thali, Ph.D. Core Facilties Faculty Advisors [unreadable]Proteomics and mass spec. [unreadable]Dwight Matthews, Ph.D. [unreadable]Microarray and Bioinformatics [unreadable]Jeffrey Bond, Ph.D. [unreadable]Administrative Core [unreadable]Ralph Budd, M.D. A closely related effort has been renewed interest in factors that influence immune memory, in anticipation of vaccine design as a logical outcome of our collaborative efforts. Specific signaling pathways in this area include the four histamine receptors (Dr. Teuscher's group has identified upregulation of H3R only on memory T cells), IL-6 promotion of IL-21, a B cell memory cytokine (Dr. Rincon), and caspase regulation of effector T cell survival (Dr. Budd). Of note is that the junior faculty contain three women and two physician/scientists. Furthermore, four of the infectious agents studied by the junior investigators in this proposal are either Category A (flavivirus) or Category B (Cryptosporidium parvum, Entamoeba histolytica, and Toxoplasma gondii) on the NIH/CDC list of Priority Pathogens. During the past year two new junior faculty joined the COBRE group and one "graduated" due to receipt of an R01 grant. Dr. Jason Botten, Assistant Professor of Medicine, came from the Scripps Research Institute. Dr. Botten works on the immune response to flaviviruses and arenaviruses. Dr. Jane Hill, Assistant Professor of Engineering, came from Yale University and joined the College of Engineering. Dr. Hill has expertise in mass spec and is investigating methods of detecting aerosolized microbial products. Dr. Jonathan Boyson, (Molecular Determinants of iNKT Cell Activation by CD1 and Its Ligands), Assistant Professor of Surgery, received a new R01 grant and has now transitioned to being a mentor. In addition, Dr. Terrance Delaney, (Regulation and Effectors of Plant Innate Immunity) Associate Professor of Plant Biology, received tenure this past year and will thus "graduate" from junior investigator to mentor later this summer. We are actively recruiting two additional new faculty members to the Vermont Center for Immunology and Infectious DIseases. One will likely be a Ph.D. who will join the Department of Microbiology and Molecular Genetics, while the other will hopefully be an M.D. and will join the Department of Medicine in the Infectious Diseases Unit. An additional area of development is to plan for a new BSL3 facility, initially with in vitro capacity, and later a BSL3 animal facility. Dr. Botten has need of an in vitro BSL3 facility for his work on arenaviruses, Dr. Beth Kirkpatrick may initiate a collaboration with a local company that wants to develop infrared detection of level 3 organisms, and one of our candidates for the new faculty position works with a level 3 agent. Given the expense of such facilities, combined with the limited resources of UVM, we have initiated several avenues to raise the needed funds. The first will be a T1 supplement request to the COBRE grant, under the ARRA program. The second would be a standard G20 application. The third is to initiate discussions with the Vermont State Health Department in a potential partnership on a new BSL3 facility, as the state has need to replace its aging BSL3 facility. This alliance with the State Health Department is one that we have been developing even before the mutual need for a new BSL3 facility arose. We have had several meetings with state representatives and this project is moving forward. At an organizational level, we continue our weekly joint laboratory meeting at which all COBRE investigators and their laboratory students/postdoctoral fellows present their work-in-progress. This brings together faculty from the disciplines of immunology, infectious diseases, microbial pathogenesis, plant defense, and bioengineering for a weekly venue at which to share our research. As director I have intentionally stressed the overlapping interests of the microbiologists and immunologists over common themes. The reason for this is not only the obvious realization that the immune system is present primarily to fight infection, but also that the most interesting and important breakthroughs in cell biology have almost always occurred at the interface between disciplines. From this initiative comes the very clear expectation that these collaborative interactions will result in collaborative R01s, a new P01 Program project Grant application, and an expanded number of training slots on our T32 Training grant (currently only 2 slots funded). The areas of overlap have included the contributions of bacterial products in triggering Toll-like receptors (Borrelia burgdorferi triggering of TLR2, Drs. Budd and Teuscher;Coxsackievirus triggering of TLR3, Dr. Huber, and plant defensins, Dr. Delaney), NOD family members (Entamoeba triggering of caspase-mediated death of macrophages, Dr. Huston, and anthrax killing of macrophages via Nalp1b by Dr. Teushcer), CD1 triggering of NKT cells (Drs. Boyson and Bonney), and HIV, Borrelia and Cryptosporidium triggering of gd T cells (Drs. Thali, Budd, and Kirkpatrick). A closely related effort has been renewed interest in factors that influence immune memory, in anticipation of vaccine design as a logical outcome of our collaborative efforts. Specific signaling pathways in this area include the four histamine receptors (Dr. Teuscher's group has identified upregulation of H3R only on memory T cells), IL-6 promotion of IL-21, a B cell memory cytokine (Dr. Rincon), and caspase regulation of effector T cell survival (Dr. Budd). A third research theme that has begun to attract our attention is the possibility of autoimmune reactions as a result of the response to infectious agents. These have included the role of NKT cells in autoimmune hepatitis, given the co-localization of CD1d expression and resident NKT cells in the liver (Dr. Boyson), how dysregulated T cell homeostatic proliferation during pregnancy (Dr. Bonney) or in the absence of Fas (Dr. Budd) might augment autoimmune diatheses, and the influence on the number of CD4+CD25+ Treg by either Coxsackievirus infection (Dr. Huber) or day 3 thymectomy (Dr. Teuscher). As a result of our most recent retreat, we have also formed a research interest around the RNA sensor RIG-I helicases, as our group is studying many RNA viruses, including the arenaviruses, coxsackievirus, LCMV, and influenza. In the spirit of fostering new interdisciplinary research efforts, we conducted our third COBRE retreat in March, 2009. This time, since faculty were quite familiar with individual lab research themes, and had already begun some collaborations, I elected to have this year's retreat centered around potential themes for P01 Program Project Grants. Four models were presented in the morning, each with its own leader. In the afternoon we broke up into groups to discuss details of how interested investigators might fit into a given theme. This has proved quite helpful and is now launching us toward one of our major goals of submitting collaborative R01 or P01 applications in the future. We have continued our COBRE seminar series in Immunology/Infectious Diseases. We have invited investigators who, for the most part, are studying the immune response to infectious agents. The list of speakers to date includes: Visiting Professors for Immunobiology Seminars -- 07/01/08 - 06/30/09 Name/Institution: Host: Date: Sheng-Yang He Terry Delaney 9/5/08 Michigan State Univ. Jen Sheen Terry Delaney 10/3/08 Harvard - Boston MA Dennis Kasper Cory Teuscher 10/10/08 Harvard - Boston MA Greg Burton Cory Teuscher 10/31/08 Brigham Young Univ Anthony Sinai Chris Huston 11/7/08 Univ. of KY Andrew Lichtman Sally Huber 2/13/09 Harvard Sabra Klein Sally Huber 2/27/09 Johns Hopkins Gary Winslow Ralph Budd 3/13/09 University at Albany Linda Cauley Mercedes Rincon 4/17/09 UCONN Marcelo Sztein Beth Kirkpatrick 6/5/09 University of Maryland Evaluation We met with our External Advisory Committee (EAC) in October, 2008 for the second of our annual meetings with the EAC. The format for this retreat was the traditional presentation of each research project by the six junior investigators, the two core facilities, with an overview presentation by the director (Dr. Budd) and Co-Director (Dr. Ward). Our EAC members include Dr. Roger Davis (UMass), Dr. Eric Pamer (Sloan Kettering), Dr. William Petri (U. Virginia), Alan Sher (NIH), and ex officio, Dr. Donald Capre, who is both an alum of UVM, a world-renowned immunologist and former director of the Oklahoma Medical Research Foundation, and a former COBRE director. The review by our EAC is included. At the global level, their remarks included many laudatory comments regarding the synergism of the group, the importance of the theme, and the leadership. Two institutional items needed attention. The first was that the COBRE program had not yet received its assignment of laboratory space for new faculty recruits. Dr. Budd is working with College of Medicine Administration to hopefully resolve this issue. We do not believe this will impede our current recruitment process as both the Departments of Medicine and Microbiology and Molecular Genetics have kindly offered laboratory space. The second issue was the need to protect the research time of the junior faculty, particularly of our physician-scientists. The EAC recommended that when a junior faculty member receives an R01 grant, that the COBRE not withdraw funds, but rather allow them to use the funds to build a second research project unrelated to the R01 grant. Both the junior and senior faculty are very much in favor of this, and work closely with the administration to insure that this translates directly into increased protected time. New Faculty Recruitment We are in the midst of a recruitment effort for two new faculty to join the COBRE team in the Vermont Center for Immunology/Infectious Diseases. We have completed all first round interviews and will decide within the next week which candidates will be invited back for a second visit. Last summer we completed our first new faculty recruit, Dr. Jason Botten, who arrived from Scripps Research Institute on July 1, 2008. Dr. Botten is an expert in the study of arenaviruses (hantavirus, lassa virus, LCMV) and is mapping immunodominant epitopse of these viruses in humans for eventual vaccine design. Education In the area of education we have begun two initiatives. The first is a new graduate education track in Immunology/Microbiology as part of UVM's new umbrella program in Cell and Molecular Biology. This is a direct result of the critical mass of investigators in this area that now exist at UVM, a direct result of the COBRE grant. As part of this initiative, we are developing a new curriculum for graduate students in this track. We started the first UVM-credited graduate seminar in advanced immunology two years ago and will continue that. In collaboration with the Vermont Lung Center COBRE, we offered joint seminar series in grant writing, laboratory management skills, and transgenic mice. Finally, we have continued to provide funding for two senior graduate students, Mr. Rajkumar Noubade in Dr. Teuscher's laboratory, and Ms. Ketki Hatle in Dr. Rincon's laboratory. Both Mr. Noubade and Ms Hatle have recently successfully defended their theses and will move off the COBRE grant and be replaced by a new senior graduate student. We also began support for a postdoctoral fellow, Dr. Andreas Koenig, in Dr. Budd's laboratory. Additional areas of accomplishment have been made in publications, including 17 from junior faculty and 53 from senior faculty. Among these, Dr. Rincon published an article in Science in 2008 that describes a new function for p38 in phosphorylating GSK3b. Grants by junior faculty now include an R01 to Dr. Boyson, and a Young Investigator's Award to Dr. Huston from the American Society for Clinical Investigation as well as a new R01 grant to Dr. Huston. Dr. Kirkpatrick was one of two finalist in a large center grant application to NIAID to be designated an NIH vaccine testing center. Although her group was not the final winner, to have been one of two finalists was enormously helpful to get her name known at NIAID. As a result of this recognition, Dr. Kirkpatrick was invited to join a dengue vaccine center grant that was just awarded to Johns Hopkins. Among senior faculty, Dr. Budd received a 5-year renewal of his R01 grant studying gd T cells in Lyme arthritis, and Dr. Teuscher received a new R01 grant to examine genes associated with autoimmunity on the Y chromosome. Other accomplishments include Dr. Budd, the PI, being named a University Scholar at UVM for 2009-2010. As a result of all these combined efforts, the Vermont Center for Immunology and Infectious Diseases has been recognized as a center of excellence by the College of Medicine. This has been recognized by our new Dean, Dr. Frederick Morin. Thus, we have come a remarkable long way since the inception of the Immunobiology Program 14 years ago with one founding member. Summary of continuing accomplishments during the current funding period [unreadable]Joint weekly laboratory meetings [unreadable]Seminar series of outside speakers [unreadable]Offering of new courses in advanced immunology, grant writing skills, laboratory management skills, and transgenic mice [unreadable]Recruitment of the first of three new faculty in the areas of immunology and infectious diseases (Dr. Jason Botten) [unreadable]Hosting of the 4th COBRE retreat to form themes for collaborative research [unreadable]Awarding of a subcontract for an NIH-funded dengue vaccine trial by Dr. Kirkpatrick [unreadable]Appointment of Dr. Budd as a UVM University Scholar [unreadable]Publication of several high profile manuscripts, including one in Science Future Directions During the fourth year of funding, we will concentrate on : [unreadable]recruitment of two additional new faculty [unreadable]initiating the collaborations that formed as a result of our "challenge talks" and recent retreat [unreadable]developing the new graduate student track in immunology [unreadable]Development of a joint BSL3 facility plan with the Vermont State Health Department